ENZYMATIC GLUCURONIDATION OF A NOVEL CHOLESTEROL ABSORPTION INHIBITOR, SCH-58235

A glucuronide of a novel cholesterol absorption inhibitor was synthesi zed on a 200-mg scale in one step via bovine liver glucuronyltransfera se-catalyzed coupling of the glucuronyl moiety of UDP-glucuronic acid with the phenolic hydroxyl of Sch 58235. It was shown that the product yield is limited by the hydrolysis of UDP-glucuronic acid by impuriti es present in the commercial microsomal preparation of the transferase . This detrimental effect of UDPGluA hydrolysis could be diminished by the presence of high concentration of glucuronlytransferase. Optimiza tion of reaction conditions and purification procedure resulted in a p rocess that proceeded with 95% conversion and 88% isolated product yie ld. The C-13(6)-glucuronide of Sch 58235 was prepared with the help of a cascade of eight enzymes operating concurrently in one pot.